Impact of serial systemic infection on Candida albicans virulence factors

2020 ◽  
Vol 15 (13) ◽  
pp. 1249-1263
Author(s):  
Glaucia S Arita ◽  
Daniella R Faria ◽  
Karina M Sakita ◽  
Franciele AV Rodrigues-Vendramini ◽  
Isis RG Capoci ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Murine Model ◽  
Systemic Infection ◽  
Systemic Candidiasis ◽  
Fungal Burden ◽  
Histopathological Findings ◽  
Phenotypic Profile ◽  
Proteomic Data ◽  
Repeated Contact

Aim: To evaluate changes in virulence and pathogenicity approaches from Candida albicans after successive passages in a murine model of systemic candidiasis. Materials & methods: Phenotypic assays were performed using colonies recovered from animals infected serially, totalizing five passages. Results: A progressive infection was observed along the passages, with increased fungal burden and the presence of greater inflammatory areas in the histopathological findings. Recovered strains exhibited increased filamentation and biofilm abilities, along with modulation of phospholipase and proteinase activities. Conclusion: Repeated contact between yeast and host increased the expression of virulence factors. Furthermore, a correspondence between phenotypic profile and proteomic data obtained previously was observed.

scholarly journals Ibuprofen Potentiates theIn VivoAntifungal Activity of Fluconazole against Candida albicans Murine Infection

2015 ◽  
Vol 59 (7) ◽  
pp. 4289-4292 ◽  
Author(s):  
Sofia Costa-de-Oliveira ◽  
Isabel M. Miranda ◽  
Ana Silva-Dias ◽  
Ana P. Silva ◽  
Acácio G. Rodrigues ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Murine Model ◽  
Resistant Strain ◽  
Efflux Pump ◽  
Systemic Infection ◽  
New Approach ◽  
Content Type ◽  
Fungal Burden ◽  
Fluconazole Resistant

ABSTRACTCandida albicansis the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression.

scholarly journals Unaltered Fungal Burden and Lethality in Human CEACAM1-Transgenic Mice During Candida albicans Dissemination and Systemic Infection

2019 ◽  
Vol 10 ◽  
Author(s):  
Esther Klaile ◽  
Mario M. Müller ◽  
Cristina Zubiría-Barrera ◽  
Saskia Brehme ◽  
Tilman E. Klassert ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Transgenic Mice ◽  
Systemic Infection ◽  
Fungal Burden

scholarly journals Antimicrobial Photodynamic Inactivation Inhibits Candida albicans Virulence Factors and ReducesIn VivoPathogenicity

2012 ◽  
Vol 57 (1) ◽  
pp. 445-451 ◽  
Author(s):  
Ilka Tiemy Kato ◽  
Renato Araujo Prates ◽  
Caetano Padial Sabino ◽  
Beth Burgwyn Fuchs ◽  
George P. Tegos ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Sodium Dodecyl ◽  
Systemic Infection ◽  
Tube Formation ◽  
Photodynamic Inactivation ◽  
Content Type ◽  
Daughter Cells

ABSTRACTThe objective of this study was to evaluate whetherCandida albicansexhibits altered pathogenicity characteristics following sublethal antimicrobial photodynamic inactivation (APDI) and if such alterations are maintained in the daughter cells.C. albicanswas exposed to sublethal APDI by using methylene blue (MB) as a photosensitizer (0.05 mM) combined with a GaAlAs diode laser (λ 660 nm, 75 mW/cm2, 9 to 27 J/cm2).In vitro, we evaluated APDI effects onC. albicansgrowth, germ tube formation, sensitivity to oxidative and osmotic stress, cell wall integrity, and fluconazole susceptibility.In vivo, we evaluatedC. albicanspathogenicity with a mouse model of systemic infection. Animal survival was evaluated daily. Sublethal MB-mediated APDI reduced the growth rate and the ability ofC. albicansto form germ tubes compared to untreated cells (P< 0.05). Survival of mice systemically infected withC. albicanspretreated with APDI was significantly increased compared to mice infected with untreated yeast (P< 0.05). APDI increasedC. albicanssensitivity to sodium dodecyl sulfate, caffeine, and hydrogen peroxide. The MIC for fluconazole forC. albicanswas also reduced following sublethal MB-mediated APDI. However, none of those pathogenic parameters was altered in daughter cells ofC. albicanssubmitted to APDI. These data suggest that APDI may inhibit virulence factors and reducein vivopathogenicity ofC. albicans. The absence of alterations in daughter cells indicates that APDI effects are transitory. The MIC reduction for fluconazole following APDI suggests that this antifungal could be combined with APDI to treatC. albicansinfections.

scholarly journals Efficacies of Fluconazole, Caspofungin, and Amphotericin B in Candida glabrata-Infected p47phox−/− Knockout Mice

2002 ◽  
Vol 46 (5) ◽  
pp. 1240-1245 ◽  
Author(s):  
Justina Y. Ju ◽  
Cynthia Polhamus ◽  
Kieren A. Marr ◽  
Steven M. Holland ◽  
John E. Bennett
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Murine Model ◽  
Knockout Mice ◽  
Candida Glabrata ◽  
Drug Efficacy ◽  
Fungal Burden ◽  
Lethal Infection

ABSTRACT Candida glabrata is the second leading cause of adult candidemia, resulting in high mortality. Amphotericin B is considered the treatment of choice, while the efficacy of fluconazole is controversial and caspofungin efficacy is unknown. To ascertain drug efficacy in vivo, the utility of a murine model of C. glabrata infection was investigated. C. glabrata was found to cause progressive, lethal infection when injected intravenously into C57BL/6 mice with reduced oxidative microbicidal capacity due to knockout of the p47phox gene. Spleen and kidney organ CFU counts were determined in groups of mice 2 days after the mice completed 6 days of daily intraperitoneal drug treatment, which began on the day of infection. Daily injections of fluconazole at 80 mg/kg did not reduce spleen or kidney CFU counts after infection with C. glabrata strains having in vitro fluconazole MICs of 2, 32, or 256 μg/ml compared to saline-treated controls. However, this fluconazole regimen reduced spleen CFU counts in mice infected with Candida albicans, an infection that is known to be responsive to fluconazole. Caspofungin at 5 mg/kg and amphotericin B at 5 mg/kg were both effective in reducing fungal burden in spleens and kidneys of C. glabrata-infected mice. Ten mice treated for 6 days with caspofungin at 1 mg/kg survived for 15 days, though all 10 saline-injected mice died or were so ill that they had to be sacrificed by 96 h postinfection. This murine model provided evidence of the efficacy of amphotericin B and caspofungin but not of fluconazole against C. glabrata infection.

scholarly journals Anidulafungin Treatment of Candidal Central Nervous System Infection in a Murine Model

2009 ◽  
Vol 53 (8) ◽  
pp. 3576-3578 ◽  
Author(s):  
Cheol-In Kang ◽  
Mark S. Rouse ◽  
Jayawant N. Mandrekar ◽  
James M. Steckelberg ◽  
Robin Patel
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Candida Albicans ◽  
Brain Tissue ◽  
Amphotericin B ◽  
Murine Model ◽  
Potential Role ◽  
Central Nervous System Infection ◽  
Cns Infection ◽  
Fungal Burden

ABSTRACT We established a murine model of Candida albicans central nervous system (CNS) infection and evaluated the efficacy of anidulafungin. Ten milligrams/kg/day anidulafungin, amphotericin B, or voriconazole significantly reduced mortality and fungal burden in brain tissue, although amphotericin B and 10 mg/kg/day anidulafungin reduced fungal burden in brain tissue to a greater extent than did voriconazole. This suggests a potential role for anidulafungin in the treatment of candidal CNS infection.

scholarly journals Efficacy of granulocyte transfusions in the control of systemic candidiasis in the leukopenic host

Blood ◽  
1978 ◽  
Vol 52 (3) ◽  
pp. 493-498 ◽  
Author(s):  
RC Ruthe ◽  
BR Andersen ◽  
BL Cunningham ◽  
RB Epstein
Keyword(s):  
Body Weight ◽  
Candida Albicans ◽  
Systemic Infection ◽  
Canine Model ◽  
Systemic Candidiasis ◽  
Quantitative Culture ◽  
Culture Techniques ◽  
Granulocyte Count ◽  
Experimental Canine ◽  
And Control

An experimental canine model was designed to evaluate the effect of granulocyte transfusions on systemic infection with Candida albicans in the granulocytopenic host. Each of a pair of dogs was rendered granulocytopenic with a single intravenous (i.v.) dose of cyclophosphamide (50 mg/kg body weight) and challenged with 10(6) Candida albicans organisms administered i.v. when granulocyte counts were less than or equal to 500/mm3. Granulocytes procured by leukofiltration were infused into six experimental dogs 1, 24, 48, and 72 hr after challenge with Candida. An average of 13 +/- 1.3 X 10(9) granulocytes were administered per infusion, producing an average 1-hr increment of 588 +/- 146 granulocytes/mm3 over the pretransfusion granulocyte count. Experimental and control dogs were killed 96 hr after challenge and organs examined grossly and by quantitative culture techniques to measure the extent of infection. All animals receiving granulocyte transfusions had significantly less tissue infection than nontransfused controls (p less than 0.05). It was concluded that granulocyte transfusions are effective in reducing the severity of infection by Candida albicans during periods of leukopenia.

scholarly journals Efficacy of granulocyte transfusions in the control of systemic candidiasis in the leukopenic host

Blood ◽  
1978 ◽  
Vol 52 (3) ◽  
pp. 493-498 ◽  
Author(s):  
RC Ruthe ◽  
BR Andersen ◽  
BL Cunningham ◽  
RB Epstein
Keyword(s):  
Body Weight ◽  
Candida Albicans ◽  
Systemic Infection ◽  
Canine Model ◽  
Systemic Candidiasis ◽  
Quantitative Culture ◽  
Culture Techniques ◽  
Granulocyte Count ◽  
Experimental Canine ◽  
And Control

Abstract An experimental canine model was designed to evaluate the effect of granulocyte transfusions on systemic infection with Candida albicans in the granulocytopenic host. Each of a pair of dogs was rendered granulocytopenic with a single intravenous (i.v.) dose of cyclophosphamide (50 mg/kg body weight) and challenged with 10(6) Candida albicans organisms administered i.v. when granulocyte counts were less than or equal to 500/mm3. Granulocytes procured by leukofiltration were infused into six experimental dogs 1, 24, 48, and 72 hr after challenge with Candida. An average of 13 +/- 1.3 X 10(9) granulocytes were administered per infusion, producing an average 1-hr increment of 588 +/- 146 granulocytes/mm3 over the pretransfusion granulocyte count. Experimental and control dogs were killed 96 hr after challenge and organs examined grossly and by quantitative culture techniques to measure the extent of infection. All animals receiving granulocyte transfusions had significantly less tissue infection than nontransfused controls (p less than 0.05). It was concluded that granulocyte transfusions are effective in reducing the severity of infection by Candida albicans during periods of leukopenia.

Chlamydospore-like cells of Candida albicans in the gastrointestinal tract of infected, immunocompromised mice

1991 ◽  
Vol 37 (8) ◽  
pp. 637-646 ◽  
Author(s):  
G. T. Cole ◽  
K. R. Seshan ◽  
M. Phaneuf ◽  
K. T. Lynn
Keyword(s):  
Candida Albicans ◽  
Murine Model ◽  
Immunological Response ◽  
Cortisone Acetate ◽  
Systemic Candidiasis ◽  
Gi Tract ◽  
Electron Microscopic ◽  
Immunocompromised Mice

We have demonstrated in a previously described murine model of gastrointestinal (GI) and systemic candidiasis that the antifungal angent cilofungin was efficacious in clearing infection of body organs when administered subcutaneously by infusion, but permitted large numbers of Candida albicans in the GI tract to persist. Yeast and hyphae in these animals were associated primarily with the stratified squamous epithelium of the stomach. Administration of immunocompromising drugs (cyclophosphamide plus cortisone acetate) to animals with persistent GI infection resulted in relapse of systemic candidiasis. Histological examination of the gastric mucosa revealed invasive hyphal elements and yeast as well as multiple chlamydospore-like cells. Comparative histochemical and electron-microscopic examinations of these latter cells produced in host tissue and chlamydospores formed in vitro were conducted. The results suggested that similarities in wall and cytoplasmic composition and ultrastructure exist between these in vivo and in vitro produced C. albicans cells. Exposure of C. albicans to cyclophosphamide during in vitro growth resulted in stimulation of chlamydospore production. No significant effect of cortisone acetate on C. albicans morphogenesis was detected. The murine model used in this study permits investigation of the formation of chlamydospore-like cells of C. albicans during early stages of fungal invasion of cyclophosphamide-treated mice, and of the possible influence of these cells on immunological response of the host to persistent candidiasis of the GI tract. Key words: Candida albicans, chlamydospores, gastrointestinal candidiasis, cyclophosphamide.

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